Modified Anti-CD3 Therapy in Psoriatic Arthritis: A Phase I/II Clinical Trial

TAMMY O. UTSET, JULIE A. AUGER, DONNA PEACE, ROBERT A. ZIVIN, DANLIN XU, LINDA JOLLIFFE, MARIA-LUISA ALEGRE, JEFFREY A. BLUESTONE, and MARCUS R. CLARK

ABSTRACT.

Objective. Treatment of autoimmune diseases with therapies that tolerize pathogenic lymphocytes may obviate the need for longterm global immunosuppression. In vitro, non-Fc receptor binding derivatives of anti-murine CD3 monoclonal antibodies tolerize type 1 T cells and stimulate type 2 T cells. Recently, a humanized non-FcR binding derivative of the anti-human CD3 Mab OKT3, huOKT3g1(ala-ala), has been described. We hypothesized that this Mab may be safe and efficacious in the treatment of type 1 T lymphocyte mediated chronic autoimmune diseases such as psoriatic arthritis (PsA).

Methods. In a Phase I/II trial, 7 patients with PsA were treated with escalating daily doses of huOKT3g1(ala-ala) for 12 to 14 days. Number of tender and swollen joints and a visual analog pain scale were used to rate disease activity at entry and Day 30 and Day 90 after treatment.

Results. At Day 30, 6 of 7 patients had ³ 75% improvement in the number of inflamed joints and an average 63% improvement on the patient pain scale. Two of 6 responders had sustained improvement at Day 90. No patient treated with an initial dose £ 1 mg had significant side effects, nor did they have detectable increases in serum cytokines. One patient treated with 4 mg without escalation developed mild cytokine release symptoms associated with elevation of interleukin 10. Transient T cell depletion occurred following treatment with the maximum dose of 4 mg, which resolved by Day 30. Antiidiotypic antibodies developed in 2 patients; however, there was no concurrent decrease in efficacy.

Conclusion. These data indicate that huOKT3g1(ala-ala) may be useful in treating PsA. (J Rheumatol 2002;29:1907-13)

Key Indexing Terms:

PSORIATIC ARTHRITIS
SPONDYLOARTHROPATHY
MONOCLONAL ANTIBODY
OKT3
CLINICAL TRIAL

---

From the Section of Rheumatology, The Ben May Institute for Cancer Research, and the Section of Transplant Surgery, University of Chicago, Chicago, Illinois; Johnson and Johnson Laboratories, Raritan, New Jersey; and UCSF Diabetes Center, University of California, San Francisco, San Francisco, California, USA.

This study was fully funded by a grant from the University of Chicago General Clinical Research Center, which is supported by the National Center for Research Resources (M01-RR00055).

T.O. Utset, MD, MPH, Assistant Professor; M.L. Alegre, MD, PhD, Assistant Professor; M.R. Clark, MD, Associate Professor, Section of Rheumatology, University of Chicago; J.A. Auger, BS, The Ben May Institute for Cancer Research; D. Peace, BS, Section of Transplant Surgery, University of Chicago; R.A. Zivin, PhD; D. Xu, PhD; L. Jolliffe, PhD, Johnson and Johnson Laboratories; J.A. Bluestone, PhD, Professor, UCSF Diabetes Center, University of California, San Francisco.

Dr. Bluestone has a financial interest in the monoclonal antibody hOKT3gamma1 (ala-ala) consisting of a patent application and a commercial agreement with Centocor/Johnson & Johnson.

Address reprint requests to Dr. M. Clark, 5841 S. Maryland Avenue, MC 0930, Chicago, IL 60637. E-mail: mclark@medicine.bsd.uchicago.edu

Submitted August 7, 2001; revision accepted March 11, 2002.

---